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Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
158 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
10
Modified dose descriptor starting point:
NOAEC
Value:
1 579 mg/m³
Explanation for the modification of the dose descriptor starting point:
No inhalative study is available because its necessity was not identified as the substance has a low vapour pressure and large particle size, so not inhalable forms will be formed. So, the most relevant study for the mandatory derivation of this DNEL (Workers, inhalation, systemic effects, long-term) is a chronic (2 a) oral toxicity study on both rats and mice.
AF for dose response relationship:
1
Justification:
default
AF for differences in duration of exposure:
1
Justification:
default (NOAEC is derived from a chronic study study)
AF for interspecies differences (allometric scaling):
1
Justification:
no allometric scaling is needed for oral-to-inhalation extrapolation
AF for other interspecies differences:
2
Justification:
In this chronic study, already two species were tested and the NOAEC is derived from the more sensitive species, so the uncertainty of interspecies extrapolation is already reduced compared to the default AF
AF for intraspecies differences:
5
Justification:
default
AF for the quality of the whole database:
1
Justification:
default (good quality of the database)
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties are identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
8.57 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
70
Modified dose descriptor starting point:
NOAEL
Value:
600 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
No long-term study on dermal toxicity is available and required, so only oral toxicity data can used.
AF for dose response relationship:
1
Justification:
in accordance with the principles given in ECHA guidance R.8.
AF for differences in duration of exposure:
1
Justification:
No additional AF needs to be applied since the NOAEL is derived from a chronic study. AF is based on correction for working exposure, i.e. 40 years instead of 75 year life span (=40/75) and 8h instead of 24 exposure (=8/24)
AF for interspecies differences (allometric scaling):
7
Justification:
default factor for allometric scaling (mouse to human) as given in ECHA guidance R.8
AF for other interspecies differences:
2
Justification:
In this chronic study, already two species were tested and the NOAEC is derived from the more sensitive species, so the uncertainty of interspecies extrapolation is already reduced compared to the default AF
AF for intraspecies differences:
5
Justification:
default factor as given in ECHA guidance R.8
AF for the quality of the whole database:
1
Justification:
no AF needed since database is of high quality
AF for remaining uncertainties:
1
Justification:
no remaining uncertainties
Acute/short term exposure
Hazard assessment conclusion:
no DNEL required: short term exposure controlled by conditions for long-term
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
26.1 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
20
Modified dose descriptor starting point:
NOAEC
Value:
521.7 mg/m³
Explanation for the modification of the dose descriptor starting point:
No inhalative study is available because its necessity was not identified as the substance has a low vapour pressure and large particle size, so not inhalable forms will be formed. So, the most relevant study for the mandatory derivation of this DNEL (General population, inhalation, systemic effects, long-term) is a chronic (2 a) oral toxicity study on both rats and mice.
AF for dose response relationship:
1
Justification:
default
AF for differences in duration of exposure:
1
Justification:
default (NOAEC is derived from a chronic study study)
AF for interspecies differences (allometric scaling):
1
Justification:
no allometric scaling is needed for oral-to-inhalation extrapolation
AF for other interspecies differences:
2
Justification:
In this chronic study, already two species were tested and the NOAEC is derived from the more sensitive species, so the uncertainty of interspecies extrapolation is already reduced compared to the default AF
AF for intraspecies differences:
10
Justification:
default
AF for the quality of the whole database:
1
Justification:
default (good quality of the database)
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties are identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
4 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
140
Modified dose descriptor starting point:
NOAEL
Value:
600 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
No long-term study on dermal toxicity is available and required, so only oral toxicity data can used.
AF for dose response relationship:
1
Justification:
in accordance with the principles given in ECHA guidance R.8.
AF for differences in duration of exposure:
1
Justification:
no AF required, available NOAEL already derived from chronic (life-time) study
AF for interspecies differences (allometric scaling):
7
Justification:
default factor for allometric scaling (mouse to human) as given in ECHA guidance R.8
AF for other interspecies differences:
2
Justification:
In this chronic study, already two species were tested and the NOAEC is derived from the more sensitive species, so the uncertainty of interspecies extrapolation is already reduced compared to the default AF
AF for intraspecies differences:
10
Justification:
default factor as given in ECHA guidance R.8
AF for the quality of the whole database:
1
Justification:
no AF needed since database is of high quality
AF for remaining uncertainties:
1
Justification:
no uncertainties remaining
Acute/short term exposure
Hazard assessment conclusion:
no DNEL required: short term exposure controlled by conditions for long-term
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
4.3 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
140
Modified dose descriptor starting point:
NOAEL
Value:
600 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Not applicable - NOAEL from chronic oral study
AF for dose response relationship:
1
Justification:
default
AF for differences in duration of exposure:
1
Justification:
default (NOAEC is derived from a chronic study study)
AF for interspecies differences (allometric scaling):
7
Justification:
default
AF for other interspecies differences:
2
Justification:
In this chronic study, already two species were tested and the NOAEC is derived from the more sensitive species, so the uncertainty of interspecies extrapolation is already reduced compared to the default AF
AF for intraspecies differences:
10
Justification:
default
AF for the quality of the whole database:
1
Justification:
default (good quality of the database)
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties are identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population